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Grand Challenges is a family of initiatives fostering innovation to solve key global health and development problems. Each initiative is an experiment in the use of challenges to focus innovation on making an impact. Individual challenges address some of the same problems, but from differing perspectives.

José Castillo of Univercells in Belgium will create a compact low-cost and automated vaccine manufacturing platform by integrating three new technologies to produce more affordable vaccines at around 0.15USD per dose. Vaccine doses are generally 1-10USD most of which is due to inefficient production and high manufacturing costs including the need for major infrastructure. This relatively high cost prohibits their widespread use particularly in developing countries with limited funds. Starting with an inactivated poliovirus vaccine they will design and develop a compact high cell density bioreactor that concentrates vaccine production and high affinity capture membranes to streamline purification. They will house the technologies in a compact series of isolators that can be accommodated in a smaller laboratory space and perform pilot testing at a manufacturer's site to evaluate productivity and analyze purity and concentration of the vaccine.

Tarit Mukhopadhyay of University College London in the United Kingdom will develop a manufacturing platform to reduce the production costs of recombinant protein vaccines. Current manufacturing procedures involve serial batch operations in large complex facilities requiring highly trained operators and extensive testing and are inefficient and costly. They will build a platform that integrates and automates key steps to reduce labor costs and capital expenditure and improves product design and control procedures to reduce quality control requirements. Their aim is to maximize the number of doses with the minimal starting material leading to recombinant subunit vaccines at 0.15USD per dose rather than the current costs of several USD per dose. They will develop their approach initially using a rotavirus vaccine candidate.

Pamela Schnupf of Paris Descartes University in France will develop an oral vaccine to prevent infectious diarrhea in children by engineering a non-pathogenic bacteria to express pathogen molecules that can be safely delivered in bacterial spores. Diarrheal disease caused largely by Shigella and enterotoxigenic Escherichia coli is a major cause of morbidity and mortality in children under five years of age in low-resource settings. Segmented filamentous bacterium (SFB) is non-pathogenic and normally colonizes the human gut during infancy and stimulates the immune system to protect against infections. They will establish methods to genetically engineer SFB to express selected antigens from enterotoxigenic E.coli and test whether it can stimulate an immune response and protect against infection using established mouse models.

Michael Schrader of Vaxess Technologies Inc. in the U.S. will develop a microneedle patch that stabilizes vaccines and can deliver multiple doses through the skin at defined times thereby reducing cost waste and the need for repeat immunizations. Vaccinations delivered intradermally via microneedles are at least as effective as intramuscular delivery via injection but reduce the requirement for needles and trained health workers. The patch uses a silk fibroin protein that protects the vaccine against high temperatures removing the need for cold storage and controls the timing of release through the skin. They will refine the material for delivering two doses of inactivated poliovirus vaccine evaluate its safety and activity in animal models and optimize the manufacturing process to ensure reduced costs.

Robert GarceaUniversity of Colorado BoulderBoulder, Colorado, United States

Grand Challenges

Vaccine Manufacturing

14 Oct 2016

Robert Garcea of the University of Colorado Boulder in the U.S. will develop a method to manufacture ultrastable vaccines by coating them with nanoparticles so that multiple doses can be delivered in a single injection to reduce the costs associated with repeat immunizations and vaccine refrigeration. They have developed a method to heat-stabilize vaccines for transport and storage that involves controlled freeze-drying of antigens with adjuvants embedded in glassy organic matrices. This mixture is then coated with defined atomic layers of aluminum and additional antigens to protect the vaccines and control the release of the primer and booster vaccine at different times. They will further develop these methods to produce single-shot formulations of selected viral antigens for release at defined times and test their stability and ability to trigger a protective immune response in mice.

Denise Dunning of the Public Health Institute's Rise Up program's "Let Girls Lead" initiative in the US in collaboration with the Girls' Empowerment Network (GENET) of Malawi, and the International Center for Research on Women (ICRW) will develop and test a multi-armed approach to empower girls with information, leadership skills, and support networks to reduce the incidence of child marriage and associated harmful traditions in Southern Malawi. Malawi has one of the highest rates of child marriage in the world, with half of all girls married by the age of 18. This has serious effects on gender equity, health, and education. They will enroll 800 girls aged 14-18 years from two districts in Southern Malawi and hold weekly workshops over six-months to provide education and skills training. This will be followed by community activities initiated by the girls themselves, such as forming girl clubs and engaging male members of their families and communities to help remove the social and cultural forces that lead to child marriage.

Léger FoyetPopulation Services InternationalWashington, District of Columbia, United States

Grand Challenges

Women and Girls

11 Oct 2016

Léger Foyet of Population Services International in the U.S. along with the Organization to Advance Solutions in the Sahel (OASIS) and the High Commission of the Nigeriens Nourish Nigeriens agriculture initiative (HC3N) will improve gender equity, nutrition, and access to family planning in Niger. Niger has one of the highest levels of poverty and malnutrition. Women in Niger are usually married before the age of 16 and have on average around eight children. Men generally make the decisions on family planning, and there is limited access to contraceptives and healthcare. Non-governmental organizations have supported over 3,000 community gardens across Niger that use solar-powered drip irrigation for growing basic crops like beans. The gardens are tended daily by women, providing an opportunity to address gender inequality in a safe and supportive space. They will select up to 20 gardens to develop and test a package of successful interventions targeting both women and men including reproductive health counseling, identifying gender-based barriers to family planning, and engaging religious leaders to help overturn deep-seated social norms.

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